The central theme of the Program Project is Cellular Interactions in the Testis and the role that these interactions play in regulating germ cell differentiation. This research topic is multifaceted in that it encompasses complex cellular communications among at least four different testicular elements (Sertoli, germ, myoid, and Leydig cells). Each project director has a unique expertise and thus brings a multidisciplinary approach to the research. In project 1, Dr. Chan will extend his work on the importance of a "pregnancy specific" glycoprotein (PSG) during testis development. This glycoprotein, possibly a growth factor, is found in very high concentrations in the placenta and, more recently, Dr. Chan found that it is also present in large amounts in the mammalian testis. In project 2, Dr. Djakiew will investigate a relatively novel area of research, ie, the effect of germ cell proteins on Sertoli cell function. His preliminary results have shown that germ cell proteins regulate Sertoli cell function by stimulating total protein synthesis and secretion, and by inducing the synthesis and secretion of novel Sertoli cell peptides. He has identified a germ cell nerve growth factor-like protein which modulates a specific Sertoli cell protein, and he will concentrate on this interaction. In project 3, Dr. Dym will continue to examine the role of the Sertoli cell in the spermatogenic process. A principal objective of his research project is to use the bicameral (dual compartment) cell culture chamber to recreate the cellular elements of the testis in vitro in a manner that is analogous to their in vivo organization. In project 4, Dr. Musto will examine the mechanism by which extracellular androgen binding proteins interact with androgen-responsive cells and the response of the target cells to this interaction. It appears that a receptor-mediated endocytosis of these proteins is taking place. In project 5, Dr. Papadopoulos will continue his long-standing interest on paracrine interactions in the testis. He will investigate the mechanisms by which the Sertoli cells modulate Leydig cell function with a particular emphasis on the purification, characterization, and mechanism of action of the Sertoli cell protein(s) stimulating Leydig cell steroid biosynthesis. We are also requesting funds to establish four cores, administrative, cell culture, chemistry, and morphology and show that cost effectiveness and quality control will be enhanced. A concerted effort by several investigators with a single research theme should result in greater overall productivity, more interdisciplinary type of research, and more significant research than if each of the project directors developed their grants as independent RO1s.